March 2014

Volume 146Issue 3p593-874, e1-e19

In Memoriam

  • Thomas Russell Hendrix, MD, October 17, 1920 – December 23, 2013

    • Mark Donowitz,
    • Ted Bayless,
    • Frank Giardiello,
    • Anthony Kalloo,
    • Pankaj Jay Pasricha,
    • Linda Welch
    Published online: January 27, 2014
    The founder and first full-time Director of the Gastroenterology & Hepatology Division of the Johns Hopkins University School of Medicine died December 23, 2013 at the age of 93. Tom was an outstanding clinician, investigator, and teacher and led the Division for 31 years. Born in Ohio on October 17, 1920, Tom grew up on a farm in Tarzana, CA and he considered himself a Californian. He started at the University of California in 1938 but his studies were interrupted by being called to active duty in 1941.

Covering the Cover

  • Covering the Cover

    • Anson W. Lowe,
    • Richard H. Moseley
    Published online: January 27, 2014
    Despite the operative resection of small primary pancreatic adenocarcinomas that are without any detectable metastases, the eventual development of metastases and subsequent mortality remains the norm. This has led to hypotheses that tumor dissemination may occur at a very early stage of pancreatic cancer. In fact, studies that employed genetically defined murine models of pancreatic cancer established that preneoplastic epithelial cells circulating in the blood could be isolated even before a primary tumor could be detected (Cell 2012;148:349–361).

Mentoring, Education, and Training Corner

  • Becoming a Clinician-Educator: Lessons Learned

    • Lawrence S. Friedman
    Published online: January 24, 2014
    I always wanted to teach. My parents were high school teachers, and teaching and scholarship are in my blood. I chose medicine as my vehicle for teaching because I enjoyed helping people, wanted to remain in science, and saw that medicine would allow life-long learning and teaching at the highest level. I understood from the start that doctor in Latin means teacher.


  • Differentiating Lynch-Like From Lynch Syndrome

    • John M. Carethers
    Published online: January 27, 2014
    Lynch syndrome is a hereditary condition found in ∼3% of all colorectal cancer patients and is defined by germline inactivation in one of the DNA mismatch repair (MMR) genes (hMSH2, hMLH1, hMSH6, hPMS2).1,2 One allele is inactivated in every cell in a Lynch syndrome patient, most commonly by pathogenic mutation or deletion of hMSH2 or hMLH1, or less commonly by pathogenic mutation of hMSH6 or hPMS2. In some Lynch syndrome patients, germline deletion of the 3′ end of EPCAM (also known as TACSTD1) is found, and this deletion causes allele-specific methylation of hMSH2 that is immediately upstream from EPCAM on chromosome 2, silencing the transcription of hMSH2.
  • Hypoglycemia After Gastric Bypass: The Dark Side of GLP-1

    • Mary-Elizabeth Patti,
    • Allison B. Goldfine
    Published online: January 27, 2014
    Obesity is increasingly recognized as a major threat to individual and public health. Unfortunately, it is very difficult to achieve sustained weight loss with current medical approaches. Similarly, optimal treatment of obesity-related comorbidities, including type 2 diabetes, hypertension, nonalcoholic fatty liver disease, and cardiovascular disease remains an elusive goal for the majority of patients. Given these critical unmet needs, both clinicians and patients alike have been buoyed by the results of recent, controlled, clinical trials demonstrating potent effects of bariatric operative procedures to induce sustained weight loss and improve or normalize obesity-related comorbidities, including type 2 diabetes.
  • Combination Therapy With Methotrexate in Inflammatory Bowel Disease: Time to COMMIT?

    • Neeraj Narula,
    • Laurent Peyrin-Biroulet,
    • Jean-Frederic Colombel
    Published online: January 27, 2014
    In 2010, after years of uncertainty owing to the lack of prospective data, the SONIC study (Study of Biologic and Immunomodulator Naive Patients in Crohn's Disease) changed the therapeutic paradigm of Crohn's disease (CD) by unequivocally demonstrating in patients naive to immunosuppressive and biologic therapy with moderate-to-severe CD the superiority of combination therapy with infliximab and azathioprine over monotherapy with infliximab or azathioprine in achieving steroid-free remission and mucosal healing.
  • Biliary Cells to the Rescue of Prometheus

    • Catherine M. Verfaillie
    Published online: January 27, 2014
    From Greek mythology, we know that it was known as early as 8th century BC that the liver has an enormous regenerative capacity: Prometheus, punished by Zeus, was chained to a rock in the Caucasus, where an eagle was sent each day to feed on his liver that would grow back to be eaten again the next day. Thus, in contrast with many tissues, mature hepatocytes are capable of proliferating to replace damaged hepatocytes. However, when hepatocytes are no longer able to proliferate, “putative” progenitor cells can generate mature hepatocytes.

Gastroenterology in Motion

  • Vertical Cross-sectional Imaging of Colonic Dysplasia In Vivo With Multi-spectral Dual Axes Confocal Endomicroscopy

    • Zhen Qiu,
    • Supang Khondee,
    • Xiyu Duan,
    • ...
    • Katsuo Kurabayashi,
    • Kenn R. Oldham,
    • Thomas D. Wang
    Published online: January 17, 2014
    Pathologists evaluate histology sectioned perpendicular to the tissue surface, or in vertical cross-sections. This orientation (X–Z plane) enables evaluation of mucosal differentiation in the basilar-to-luminal direction. Current endomicroscopes use a conventional (single axis) optical design.1 Imaging is limited to horizontal cross-sections (X–Y plane) where the microanatomy is frequently similar across the field of view (FOV). In the dual axes configuration, light is delivered and collected off-axis, and images can be detected over a much larger range of intensities.
    Video Abstract

Clinical Challenges and Images in GI

  • Esophageal Stenosis Caused by a Rare Entity

    • Birte Kulemann,
    • Andreas Fischer,
    • Jens Hoeppner
    Published online: January 24, 2014
    Question: A 45-year-old man presented in our surgical department with progressive dysphagia for solids and liquids and weight loss over the last 6 month, he had a long history of tobacco abuse (25 pack-years), but no history of trauma or alcohol use. Physical examination showed his cachexia, but was otherwise unremarkable without palpable lymphadenopathy. He had been treated with long-term bouginage over 4 years for a long segment esophageal stenosis starting 30 cm distal to the dental arch. Repeatedly performed biopsies over that time course had been nondiagnostic, with only chronic inflammation and hyperkeratosis.
  • Odd-Looking Gastric Tumor

    • Krzysztof Dabkowski,
    • Maria Chosia,
    • Teresa Starzyńska
    Published online: January 27, 2014
    Question: A 73-year-old woman presented a history of epigastric discomfort over a period of 12 months. Upper endoscopy showed a small subepithelial tumor composed of 2 parts with intact covering mucosa at the gastric antrum (Figure A). She was referred to our department for endoscopic tumor resection. The physical examination, abdominal ultrasonography, colonoscopy, chest x-ray, and family history were unremarkable. Standard laboratory tests were within normal limits. An endoscopic ultrasound was performed and showed a hypoechoic tumor in the 3rd echolayer (Figure B).
  • An Unusual Complication of a Transjugular Liver Biopsy

    • Vincent Kuo,
    • Abdullah Mubarak
    Published online: January 24, 2014
    Question: A 28-year-old woman with hepatitis C presented for a liver biopsy. A transjugular approach was performed since the patient had thrombocytopenia with a platelet count of less than 50 × 103/μL. The right internal jugular vein was cannulated under ultrasound guidance and then, with fluoroscopy, a 5-french multipurpose angiographic catheter was directed via the inferior vena cava into the right hepatic vein. Three passes were made with a 19-gauge, spring-loaded needle for biopsy specimens.
  • A Woman With Melena and Transfusion-Dependent Anemia

    • Bradley Anderson,
    • Todd H. Baron,
    • Seth Sweetser
    Published online: January 24, 2014
    Question: A 47-year-old woman with hamartomatous gastric polyposis was referred for total gastrectomy because of transfusion-dependent iron deficiency anemia owing to blood loss. The patient's history included life-long, recurrent epistaxis requiring electrocautery of the nasopharynx and subtotal colectomy for juvenile colonic polyps. Physical examination revealed small telangiectasias over the bilateral cheeks and hard palate. Both the prior colectomy specimen and endoscopic gastric biopsies demonstrated juvenile hamartomatous polyps.

Electronic Clinical Challenges and Images in GI

  • Acute Dyspnea During Diagnostic Sigmoidoscopy

    • Qiyuan Qin,
    • Tenghui Ma,
    • Lei Wang
    Published online: January 27, 2014
    Question: A 29-year-old man presented with a 3-month history of intermittent diarrhea with tenesmus. He was diagnosed with Crohn’s disease and underwent subtotal colectomy and ileosigmoidostomy at an outside institution 4 years before. Sulfasalazine and mesalazine were irregularly taken during past 4 years. He denied fever, melena, hemafecia, and abdominal pain. Abdominal palpation revealed a hard and painless mass of limited motion in the left lower quadrant. Digital examination revealed the stricture of rectum.
    Online Only
  • An Unusual Endoscopic Diagnosis

    • Susana Marques,
    • Pedro Barreiro,
    • Miguel Bispo
    Published online: January 27, 2014
    Question: A 35-year-old man with no significant past medical history presented to the emergency department with intermittent right lower abdominal pain for the previous 2 weeks. Physical examination revealed mild discomfort on palpation of the right lower quadrant without any peritoneal signs. Laboratory results showed leukocytosis (14,000/μL), neutrophilia (78%), and slightly elevated C-reactive protein (CRP; 3.0 mg/dL). Abdominal ultrasonography revealed mild wall thickening in the cecum and terminal ileum and the appendix was not visualized (Figure A).
    Online Only
  • Right Upper Quadrant Pain in a 21-Year-Old Man

    • Ella Teasdale,
    • Katie E. Robertson,
    • Ewen M. Harrison
    Published online: January 27, 2014
    Question: A 21-year-old man with attention deficit hyperactivity disorder developed acute-onset, severe, right upper quadrant pain shortly after being taken into police custody. He volunteered no further past medical history or gastrointestinal symptoms other than pain. On examination, vital signs were: Heart rate, 68; blood pressure, 110/74 mmHg; temperature 37.5°C; respiratory rate, 14; and SpO2, 97% on room air. There was generalized guarding with marked rebound tenderness maximally in the right upper quadrant; electrocardiograph showed normal sinus rhythm and erect chest x-ray did not demonstrate a pneumoperitoneum.
    Online Only
  • An Uncommon Cystic Lesion of the Liver

    • Huiying Zhao,
    • Ye Li,
    • Dianbo Cao
    Published online: January 27, 2014
    Question: A 36-year-old woman was admitted to our hospital for further investigation of a cystic lesion in liver detected 6 months previously on physical examination. There were no significant symptoms. Twelve years previously, she had her appendix removed and 11 years previously, she had undergone a caesarean section. Physical examination was unremarkable except for a surgical scar in the lower abdomen. The tumor markers (alfa-fetoprotein, carcino-embryonic antigen, carbohydrate antigen [CA]-199, and CA125) were within normal limit, as were liver function tests.
    Online Only
  • An Uncommon Cause of Recurrent Duodenal Intussusception

    • Huiying Zhao,
    • Ye Li,
    • Dianbo Cao
    Published online: January 27, 2014
    Questions: A 49-year-woman was admitted to our hospital with 1-year history of intermittent black stool and epigastric pain. She occasionally experienced itchy skin and yellow sclera. Physical examination was unremarkable. Except for the decrease of hemoglobin values down to 76 g/L, all other laboratory values were within the normal limits. Endoscopy before admission showed a long, friable, ulcerated, pedicle-like structure with granular surface of the distal end, extending from the duodenal bulb into the second part of duodenum (Figure A).
    Online Only
  • An Unusual Cause of a Pancreatic Space-Occupying Lesion

    • Narendra S. Choudhary,
    • Navin Kumar,
    • Rajesh Puri
    Published online: January 27, 2014
    Question: A 57-year-old man was referred for endoscopic ultrasonography (EUS) of a pancreatic lesion. Ten years ago, he presented with epigastric pain which has since resolved. Ultrasonography at that time showed a 3-cm, solid lesion in the body of pancreas. He was advised yearly follow-up and underwent yearly ultrasonography or computed tomography of the abdomen; the lesion remained similar in size and appearance. He was recently referred for EUS of the lesion. EUS showed a 3.3-cm, solid lesion in the body of pancreas with alternating hypoechoic irregular linear areas giving it an appearance like sulci and gyri of brain (Figure A) without calcification.
    Online Only

Reviews and Perspectives

    Brief Review

    • The Clinical Consequences of Advanced Imaging Techniques in Barrett's Esophagus

      • David F. Boerwinkel,
      • Anne-Fré Swager,
      • Wouter L. Curvers,
      • Jacques J.G.H.M. Bergman
      Published online: January 13, 2014
      Evaluation of patients with Barrett’s esophagus (BE) using dye-based chromoendoscopy, optical chromoendoscopy, autofluorescence imaging, or confocal laser endomicroscopy does not significantly increase the number of patients with a diagnosis of early neoplasia compared with high-definition white light endoscopy (HD-WLE) with random biopsy analysis. These newer imaging techniques are not more effective in standard surveillance of patients with BE because the prevalence of early neoplasia is low and HD-WLE with random biopsy analysis detects most cases of neoplasia.
      Online ExtraAdditional Online Content Available

    Reviews in Basic and Clinical Gastroenterology and Hepatology

    • Hypoxia-Inducible Factors Link Iron Homeostasis and Erythropoiesis

      • Yatrik M. Shah,
      • Liwei Xie
      Published online: January 02, 2014
      Iron is required for efficient oxygen transport, and hypoxia signaling links erythropoiesis with iron homeostasis. Hypoxia induces a highly conserved signaling pathway in cells under conditions of low levels of O2. One component of this pathway, hypoxia-inducible factor (HIF), is a transcription factor that is highly active in hypoxic cells. The first HIF target gene characterized was EPO, which encodes erythropoietin—a glycoprotein hormone that controls erythropoiesis. In the past decade, there have been fundamental advances in our understanding of how hypoxia regulates iron levels to support erythropoiesis and maintain systemic iron homeostasis.

Original Research

Continuing Medical Education (CME) Activities

Consensus Statement

AGA Section

  • A Bundled Payment Framework for Colonoscopy Performed for Colorectal Cancer Screening or Surveillance

    • Joel V. Brill,
    • Rajeev Jain,
    • Peter S. Margolis,
    • ...
    • Lawrence S. Kim,
    • Laura E. Clote,
    • John I. Allen
    Published online: January 30, 2014
    With the release of the 2014 Physician Fee Schedule by the Centers for Medicare & Medicaid Services (CMS), it is clear that the substantial reductions in reimbursement for endoscopic procedures will have a profound impact on the practice of community and academic gastroenterology.1 In the Final Rule, CMS rejected the recommendations of the American Medical Association/Specialty Society Relative Value Update Committee, establishing significant reductions in physician payment for esophagoscopy, esophagogastroduodenoscopy, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography services by reducing the physician work component of the relative value units for many of the listed services.
    Online ExtraAdditional Online Content Available

Selected Summaries

Print and Digital Media Reviews

    • Whitney E. Jackson,
    • Bret Lashner
    Published online: January 27, 2014
    The authors of the board review series Acing the IBD Questions GI Board Exam, Drs Brennan Spiegel and Hetal Karsan, bring us the third of the series focusing on inflammatory bowel disease with contributing editors Drs Gil Melmed and Nir Modiano. A long-time favorite with gastroenterology fellows, this series uniquely holds our attention by presenting quick interactive clinical vignettes. The focus is on the “tough” areas of inflammatory bowel disease (IBD) that are not seen every day, but have a high likelihood of being tested on the boards.